DESCRIPTION (Taken from the applicant's Abstract) Obesity research was elevated to a new level by the recent discovery of the hormone leptin, a protein that appears to mediate both appetite and energy expenditure, and by the identification of the human OB gene, which encodes leptin. In prior studies at our laboratory we have examined three OB gene microsatellite polymorphisms (D7S514, D7S635 and D7S1875) in samples of obese and non-obese human subjects. We found that these markers were significantly associated with waist and hip measurements, body mass index (BMI), percent body fat, and two specific eating behaviors: eating when under stress, and eating when bored. However, the most robust associations were with anxiety and depression. Consistent with the literature, the anxiety/depression findings were mirrored by a genetic association with thyroid stimulating hormone (TSH), suggesting that this gene mediates eating behavior and energy via classical hypothalamic-pituitary-adrenocortical (HPA) pathways that influence psychological substrates. The proposed study will attempt to replicate and extend these findings by examining these polymorphisms in 400 new cases of obese and non-obese subjects, 200 of whom are undergoing fenfluramine/phenteramine treatment for obesity. Blood samples and assessments will be obtained both at entry to the study and at 6-month follow-up, in order to determine whether these markers are associated with treatment outcome and with changes in levels of leptin, stress, hormones and TSH.